The papillomaviruses are associated with naturally occurring carcinomas in a variety of species, including man. There are now 31 human papillomaviruses (HPVs) which have been identified in man. Four of these, HPV-6, HPV-11, HPV-16 and HPV-18, have been associated with human genital tract lesions. HPV-6 and HPV-11 have been found to be associated with a high percentge of benign genital warts, including cervical flat warts and dysplasias. HPV-16 and HPV-18 were each cloned directly from cervical carcinomas biopsy specimens and have been found in a high percentage of cervical carcinomas. We have screened a series of human carcinoma cell lines for the presence of human papillomavirus DNA sequences using HPV-6, HPV-11, HPV-16, and HPV-18 DNA probes. Six of eight cell lines which had been derived from human cervical carcinoma lines were found to contain integrated HPV DNA sequences. In five of these lines, HPV specific polyadenylated RNA species could be identified. Two of the cell lines contained integrated HPV-16 DNA and in each of these cell lines the genomes were transcriptionally active. Genomic clones have been made from these HPV-16 positive lines. Sequence analysis of the virus-host junction fragments for identification of the chromosome into which the HPV has integrated and identification of the adjacent genes is underway. While the association between specific HPVs and cervical carcinoma is strong, the mechanisms underlying any potential carcinogenic progression is unknown. Our studies are designed to identify potential mechanisms.